Research in two areas has continued, namely CD45 isoform expression during B lymphocyte and myeloid differentiation, and the effects of the mutant genes lpr and gld on T cell development and function. By PCR analysis and immunoprecipitation we showed that the 220 kDa isoform of CD45 was expressed on B lineage cells from pro-B cells to B immunoblasts. Differentiation into plasma cells was accompanied by a switch to two lower MW isoforms, a predominant species that spliced out exons 4, 5 and 6 and a minor species that spliced out exons 4, 5 and 6 early in development and retained this phenotype in mature cells. Future studies will focus on the functions of the various B lineage CD45 isoforms. To further evaluate the effects of lpr and gld on T cells we examined surface antigen expression and cytokine production by four T cell subsets. We demonstrated that a high proportion of CD4+ and CD8+ T cells expressed high levels of CD44 and reduced levels of Mel 14 and CD45R, a phenotype consistent with T cell activation. These two subsets also hypersecreted IL-2, IFN-gamma and TNF following stimulation. By comparison, the two unique B220+ T cell subsets had the phenotype of less mature T cells were refractory to stimulation and did not secrete cytokines. Future research on this project is directed toward gaining insight into the mechanisms governing the functional anergy of some lpr and gld T cell subsets and the apparent hyperactivity of others; the developmental relationships among the various T cell subsets, and the precise role of CD4+ and CD8+ T cells in the geneses of lymphoproliferative disease.